ドロソフィラ血球の発達と生存におけるノッチとHif-alphaの相互作用
Tina Mukherjee1, William Sang Kim, Lolitika Mandal
1Department of Molecular, Cell and Developmental Biology, University of California, Los Angeles, CA 90095, USA.
Science (New York, N.Y.)
|June 4, 2011
まとめ
ドロソフィラの結晶細胞は,シマ (低酸素誘導因子-α) を利用して,ノッチ信号を非正規的に活性化させ,血球の生存を向上させます. この保存されたメカニズムは,哺乳類の細胞に適用され,血液の発達とストレス反応に影響を与える可能性があります.
科学分野:
- 発達生物学 発達生物学とは
- 細胞シグナリング
- ヘマトポエーシス (血液形成) とは
背景:
- ドロソフィラの結晶細胞は,凝固と傷の治癒に不可欠であり,Notch信号を必要とします.
- 結晶細胞は,通常の酸素下でも,高いシマ (低酸素誘導因子-α) レベルを示します.
- ノルモキシアにおける低酸素誘導因子α (Hif-α) の上昇調節は,脊椎動物のミエロイド細胞で観察されています.
研究 の 目的:
- ドロソフィラの結晶細胞におけるシマ媒介のノッチ活性化の非正規的メカニズムを調査する.
- 正常および低酸素条件下における血球生存におけるこの相互作用の役割を明らかにする.
- 哺乳類におけるHif-α/Notch相互作用の潜在的保存を調査する.
主な方法:
- ドロソフィラの結晶細胞におけるシマとノッチ信号の分析.
- Hif-β (タンゴ) とその開始部位に対する相互作用の依存性を調べる.
- 研究結果を脊椎動物の骨髄状細胞の研究と比較した.
主要な成果:
- Simaは,リガンド独立の方法で全長ノッチ受容体シグナリングを活性化します.
- この非正規の経路は,発達と低酸素ストレス中に血球の生存を促進します.
- 相互作用は初期エンドソームで発生し,Hif-β (タンゴ) とは独立しています.
- 低酸素反応の標的は,このシマ-ノッチ相互作用によって活性化されません.
結論:
- 新しい非正規のHif-α/Notch経路は,ドロソフィラの血球生存を調節する.
- このメカニズムは,正規の低酸素反応とは無関係で,種ごとに保存されることがあります.
- Hif-αとNotchの相互作用のメカニズムのパラダイムを提供し,哺乳類の血液形成に潜在的に関連しています.
関連する概念動画
03:14Notch Signaling Pathway
The Notch signaling pathway is a major intracellular signaling pathway that is highly conserved over a broad spectrum of metazoan species. It stands unique from other intracellular signaling mechanisms in animals because notch protein itself acts as the receptor as well as the primary signaling molecule.
The Notch gene came into the limelight in 1914 after the discovery that its mutation in Drosophila melanogaster leads to a serrated (or "notched") wing margin phenotype. It was not until 1985...
The Notch gene came into the limelight in 1914 after the discovery that its mutation in Drosophila melanogaster leads to a serrated (or "notched") wing margin phenotype. It was not until 1985...
03:14Notch Signaling Pathway
The Notch signaling pathway is a major intracellular signaling pathway that is highly conserved over a broad spectrum of metazoan species. It stands unique from other intracellular signaling mechanisms in animals because notch protein itself acts as the receptor as well as the primary signaling molecule.
The Notch gene came into the limelight in 1914 after the discovery that its mutation in Drosophila melanogaster leads to a serrated (or "notched") wing margin phenotype. It was not until 1985...
The Notch gene came into the limelight in 1914 after the discovery that its mutation in Drosophila melanogaster leads to a serrated (or "notched") wing margin phenotype. It was not until 1985...
01:12Role Of Notch Signalling In Intestinal Stem Cell Renewal
Notch signaling was first discovered in Drosophila melanogaster, where it is involved in cell lineage differentiation. Notch signaling regulates the maintenance and differentiation of intestinal stem cells or ISCs by controlling the expression of atonal homolog 1 or Atoh1. Atoh1 directs cells to differentiate into secretory cells.
Direct cell-to-cell contact is needed for the activation of Notch signaling. The signal is initiated when a notch ligand binds to a receptor on an adjacent cell, also...
Direct cell-to-cell contact is needed for the activation of Notch signaling. The signal is initiated when a notch ligand binds to a receptor on an adjacent cell, also...
01:24Regulation of Angiogenesis and Blood Supply
Rapidly dividing tumors, embryos, and wounded tissues require more oxygen than usual, lowering the oxygen concentration in the blood. At low oxygen or hypoxic conditions, an oxygen-sensitive transcription factor called the hypoxia-inducible factor 1 or HIF1 is activated. HIF1 is a dimeric protein of alpha (ɑ) and beta (β) subunits. Under optimal oxygen conditions, HIF1β is present in the nucleus while HIF1ɑ remains in the cytosol. HIF1ɑ is hydroxylated by prolyl hydroxylase and factor...